Youssef, whose work explores themes of otherness, difference and diversity, was honoured Monday night at a ceremony at the National Arts Centre in Ottawa.
The annual prize — which recognizes playwriting, theatre design and direction in three-year cycles — also includes a protégé element: each year's recipient chooses someone to receive $25,000 of the total prize.
The Montreal-born Youssef has selected theatre artist Christine Quintana to share in his award.
The Siminovitch jury, led by chair Bob White, praised Youssef as "a mid-career artist whose work was already of the highest calibre and was, in fact, changing the face of Canadian theatre."
Youssef's plays — which have been performed across Canada, Europe and Australia — include Winners and Losers, King Arthur's Night, How Has My Love Affected You? and A Line in the Sand.
The Siminovich prize makes a "practical difference" in the lives of both nominee and winners, Youssef said.
"It honours artists in midlife, when I think many of us begin to wonder about our choice to become artists in the first place and about what may happen to us and our families as we age. The Siminovitch Prize is a bold, powerful antidote to these pressures...It honours the idea that it might make sense for us to dare to think it is legitimate to be working artists through our whole lives."
Youssef also serves as artistic director of Vancouver's Neworld Theatre, co-founded the city's artist-run production centre PL 1422 and is an adjunct professor of creative writing at the University of British Columbia.
Other shortlisted playwrights this year included Evelyne de la Chenelière, Hannah Moscovitch and Donna-Michelle St. Bernard.
Launched in 2000 in honour of scientist Lou Siminovitch and his late wife Elinore Siminovitch, the prize celebrates Canadian theatre industry leaders who have created transformative and influential work.
Past winners include Kim Collier, Ronnie Burkett and Daniel MacIvor. Jillian Keiley and Brigitte Haentjens, current heads of the National Arts Centre's English and French theatre divisions, respectively, are also past Siminovitch laureates.